Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis.

ABSTRACT: Drosophila's white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w¹¹¹⁸ mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w¹¹¹⁸ learning phenotype is also found in the w^apricot and w^coral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w¹¹¹⁸ mutants were resistant to this deficit. The w¹¹¹⁸ mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w¹¹¹⁸ learning. However, serotonin levels were not lower in the heads of the w¹¹¹⁸ mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w¹¹¹⁸ brain. We propose that the w¹¹¹⁸ learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

SUBMITTER: Myers JL 

PROVIDER: S-EPMC8657504 | biostudies-literature |

REPOSITORIES: biostudies-literature